The specific aim of this proposal is to determine the mechanism of active epithelial chloride secretion and its control, employing the isolated opercular epithelium as the primary experimental model. Presently, this tissue is the only purely chloride transporting epithelium available, which is compatible with the current methodologies employed in the study of the mechanism and control of epithelial ion transport. Two main electrophysiological approaches will be used in these studies: chamber and microelectrode preparations. They will be used in concert with isolated cell and electronmicroscopic techniques when applicable, to provide a comprehensive picture of transepithelial chloride secretion, and chloride transport in general. For the most part, the present model for chloride secretion is speculative at best, and in many respects, incomplete. These studies will attempt to confirm, complete, and expand upon the present model. The two most interesting and frequent observations on chloride secretion are its sodium dependence and regulation by intracellular cyclic-AMP. The present proposal focuses on these phenomena and other intriguing aspects of chloride secretion, which may or may not be peculiar to this preparation. In addition, by virtue of its high density of mitochondria-rich cells ("chloride cells"), the opercular epithelium may also provide insights into the role of these cells in a variety of other epithelia, including sodium transporting epithelia. Ultimately, these studies will contribute to a better understanding of salt and water metabolism, fluid formations, and osmoregulation on both the tissue and systemic levels, and the management of disorders associated with these processes.